02 Atherosclerosis Risk: What LDL, ApoB and Lp(a) Reveal

Atherosclerosis is the gradual build-up of fat and cholesterol particles in the walls of your arteries. It often starts decades before it causes any symptoms, and its most important measurable driver shows up in your blood results: the number of LDL particles, added up over time. That makes atherosclerosis risk one of the mechanisms where looking early can make the biggest difference.

Picture someone in their mid-forties. They don't smoke, their blood pressure is good, their blood sugar is unremarkable and their cholesterol is "within the normal range". They feel fit, and by every classic criterion they're healthy. Yet plaque may already have formed in their arteries without them feeling a thing. That isn't a thought experiment, but the finding of one of the largest studies on silent atherosclerosis. And that's exactly where the opportunity lies: what you see early, you can change early.

What is atherosclerosis?

Atherosclerosis is a slow remodelling of the artery wall in which cholesterol, inflammatory cells and later calcium accumulate into so-called plaques. Over the years, these plaques can narrow the arteries. If a plaque ruptures, a blood clot can form. That's how most heart attacks and many strokes happen.

A helpful image: cholesterol is vital for the body, and it travels through the blood in small transport packages called lipoproteins. LDL particles are like delivery vans bringing cholesterol to your cells. The more vans on the road, the more often one gets "stuck" in the artery wall. There it triggers an inflammatory response, and a plaque starts to grow.

What did the PESA study reveal about silent atherosclerosis?

It showed that atherosclerosis is widespread in middle-aged people, long before it causes symptoms. In the PESA study (Progression of Early Subclinical Atherosclerosis), researchers at Spain's national cardiovascular research centre CNIC in Madrid examined around 4,200 employees of a large bank. All were aged between 40 and 54 and had no cardiovascular symptoms whatsoever. Using ultrasound of the neck, abdominal and leg arteries and a CT scan of the heart, they searched specifically for plaque ¹.

The result surprised even experts: 63% of participants already had plaque, men more often than women ¹. Even among those rated as low risk by common risk calculators, it was more than half ¹. Interestingly, the most frequently affected arteries weren't the coronary arteries, but the leg arteries in the groin ¹.

A follow-up analysis went a step further and looked only at people with no classic risk factor at all: non-smokers without high blood pressure or diabetes, with cholesterol in the normal range. Here too, about half had plaque. After age and sex, LDL cholesterol was the strongest predictor, even at levels considered normal ².

And the plaque doesn't stand still. After just three years, around 40% of the people aged 40 to 50 who were examined showed marked progression ³. The results were published in leading cardiology journals and have shaped the debate about how early cardiovascular prevention should begin.

Does LDL cholesterol really cause atherosclerosis?

Yes, and it's one of the best-established findings in medicine. The European Atherosclerosis Society analysed data from more than 200 studies involving over two million people: genetic studies, observational studies and randomised treatment trials ⁴. They all point the same way. The conclusion: LDL causes atherosclerotic cardiovascular disease ⁴.

Time turns out to be particularly revealing. Risk depends not only on how high LDL is, but also on how long the arteries are exposed to raised levels ⁴. The Austrian Lipid Consensus 2026 sums it up in one line: "the earlier, the lower, the longer, the better" ⁵.

That's a real opportunity. If you know your numbers at 40 rather than 60, you've gained two decades in which things can change.

Why does "know your numbers" matter so much for your arteries?

Because atherosclerosis doesn't hurt. There's no early warning sign you can feel, which is exactly what makes the PESA findings so striking: every participant felt healthy ¹. If you want to know how your arteries are doing, you need numbers. Four reasons why this applies to this mechanism in particular:

1. Feelings can deceive. Plaque grows silently for years. Lab values are often the only early clue.
2. "Normal" doesn't automatically mean harmless. A reference range describes what's common in the population. PESA found the link between LDL and plaque even at levels within the normal range ², and the right target for you depends on your overall personal risk ⁵.
3. Some things only show up in the lab. A raised Lp(a) is inherited and causes no symptoms ⁶. Without a test, it goes unnoticed.
4. Direction matters. Because the burden adds up over the years ⁴ and plaque can progress within a few years ³, a single test says little about where your values are heading. So "know your numbers" doesn't mean knowing a number once. It means understanding your values, seeing them in context and following how they develop over the years.

Which blood tests show your atherosclerosis risk?

Several blood markers together describe how many "delivery vans" are on the road and how much strain the environment of your arteries is under. The Lipid Consensus recommends a first lipid profile as early as possible, and no later than age 18 to 20 ⁵.

Blood marker	What it shows
LDL cholesterol	The amount of cholesterol carried in LDL particles; the main target value in the guidelines 5
Non-HDL cholesterol	All potentially artery-damaging particles combined; especially informative with high triglycerides or impaired sugar metabolism 5
Apolipoprotein B (ApoB)	The number of artery-damaging particles, since each carries exactly one ApoB; useful when LDL value and particle number don't match 5
Lipoprotein(a), or Lp(a)	A particularly harmful particle whose level is almost entirely set by your genes 6
Triglycerides and HDL	Clues about fat metabolism and its link to sugar metabolism
hsCRP	A sensitive inflammation marker showing whether silent inflammation is running in the background

How high your LDL should be isn't a one-size-fits-all number. The Lipid Consensus sets target values according to your overall personal risk: for people at low risk it's below 116 mg/dl, for those at very high risk below 55 mg/dl ⁵. There are several steps in between. For people aged 40 and over, doctors estimate overall risk using the SCORE2 model, which considers age, sex, blood pressure and smoking as well as cholesterol ⁵.

Why should you have your Lp(a) measured once in your life?

Because Lp(a) is a common but little-known risk factor that a normal cholesterol test won't reveal. About one in five people has a raised level ⁵. More than 90% of it is determined by your genes, and diet or exercise barely change it ⁶. That's exactly why a single measurement in adulthood is usually enough ⁵⁶.

At first, that may not sound encouraging: a risk you can't train away. In fact, it's the opposite. If you know your Lp(a) is raised, you can tackle all the other factors more decisively, for example by aiming for a lower LDL. The knowledge is valuable for your family too, because Lp(a) is inherited ⁶. And medicines that specifically lower Lp(a) are under intensive research.

How is atherosclerosis connected to other mechanisms?

Your blood vessels aren't an isolated system. At speak23, atherosclerosis risk belongs to the Metabolic health pillar, but it's closely linked to other mechanisms:

• Insulin resistance: When sugar metabolism is disturbed, fat metabolism changes too, typically with higher triglycerides and lower HDL. In this situation, the Lipid Consensus recommends paying particular attention to non-HDL cholesterol ⁵. More on this in our article on insulin resistance.
• Silent inflammation: Plaques develop through an inflammatory response in the artery wall. A low hsCRP is therefore a good sign in the overall picture.
• Liver and kidneys: The liver regulates how much LDL circulates in the blood. And chronically reduced kidney function counts as a factor that raises cardiovascular risk in medical risk assessment ⁵. A raised LDL with otherwise unremarkable results tells a different story from the same LDL alongside rising blood sugar, a lot of belly fat and raised hsCRP.

What can you do for your arteries?

A lot, even if not every factor responds equally to lifestyle. To be honest, changing your diet usually lowers LDL only moderately. The Lipid Consensus explicitly recommends lifestyle changes for people at low risk with mildly to moderately raised LDL, but notes that above 150 mg/dl they usually aren't enough on their own ⁵. In that case, medication is often the more effective route, and that's a decision for a conversation with your doctor.

At the same time, a healthy lifestyle acts on many factors at once: blood pressure, blood sugar, triglycerides, body weight and smoking all shape overall risk. What doesn't help: European guidelines explicitly do not recommend dietary supplements or vitamins for reducing cardiovascular risk ⁷.

Here's what the path can look like with speak23:

1. Know your vascular markers in full. In the Core Health blood test, cholesterol, LDL, HDL, non-HDL, triglycerides, ApoB and hsCRP feed into the atherosclerosis risk mechanism. You can have Lp(a) measured once with the atherosclerosis prevention add-on test.
2. Make the years visible. Because the strain on your arteries adds up over time, you test 2 or 4 times a year with speak23. All results are recorded digitally and automatically, so the app shows how your LDL and particle number develop.
3. Start with three recommendations. You receive three evidence-based recommendations tailored to your blood results and your health history, such as smoking, physical activity, family history or medication. They aim to move your values in the right direction.
4. See the effect. At your next test, the app shows whether your changes are reflected in your results.
5. Factor in blood pressure and see a doctor. Blood pressure isn't a blood marker, but it belongs in the overall picture. Have it measured regularly and discuss it together with your blood results. If your LDL is above 190 mg/dl, the Lipid Consensus recommends checking for an inherited lipid disorder ⁵. For unusual results, you get specific questions to take to your doctor. speak23 doesn't replace a diagnosis. For an overview of all 12 mechanisms, read our article Understanding blood test results: why connections matter.

What could cardiovascular prevention look like in the future?

The evidence is clear: LDL is a causal factor ⁴, the burden adds up over the years ⁴⁵, plaque often starts forming in people who are healthy by classic criteria ¹², and it can progress within a few years ³. At the same time, many people don't know their numbers, and Lp(a) is still rarely measured. That's where the biggest lever lies.

We believe cardiovascular prevention could start much earlier in the future: with a full lipid profile in young adulthood, a one-off Lp(a) test and a trend line that shows how values develop over the years. Our approach at speak23 is to look at these values not in isolation, but together with metabolism, inflammation and organ health, and to support you in changing them.

Cardiovascular disease is one of the major health challenges of an ageing society. Yet there's hardly another area where the knowledge is so clear and the tools so good. The question isn't whether something can be done, but when you start. And the answer is: ideally now.

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